Sequencing paired tumor DNA and white blood cells improves circulating tumor DNA tracking and detects pathogenic germline variants in localized colon cancer.

BACKGROUND: In the setting of localized colon cancer (CC), circulating tumor DNA (ctDNA) monitoring in plasma has shown potential for detecting minimal residual disease (MRD) and predicting a higher risk of recurrence. With the tumor-only sequencing approach, however, germline variants may be misidentified as somatic variations, precluding the possibility of tracking in up to 11% of patients due to a lack of known somatic mutations. In this study, we assess the potential value of adding white blood cells (WBCs) to tumor tissue sequencing to enhance the accuracy of sequencing results. PATIENTS AND METHODS: A total of 148 patients diagnosed with localized CC were prospectively recruited at the Hospital Clínico Universitario in Valencia (Spain). Employing a custom 29-gene panel, sequencing was conducted on tumor tissue, plasma and corresponding WBCs. Droplet digital PCR and amplicon-based NGS were performed on plasma samples post-surgery to track MRD. Oncogenic somatic variants were identified by annotating with COSMIC, OncoKB and an internal repository of pathogenic mutations database. A variant prioritization analysis, mainly characterized by the match of oncogenic mutations with the evidence levels defined in OncoKB, was carried out to select specific targeted therapies. RESULTS: Utilizing paired tumor and WBCs sequencing, we identified somatic mutations in all patients (100%) within our cohort, compared to 89% using only tumor tissue. Consequently, the top 10 most frequently mutated genes for plasma monitoring were altered. The sequencing of WBCs identified 9% of patients with pathogenic mutations in the germline, with APC and TP53 being the most frequently mutated genes. Additionally, mutations in genes related to clonal hematopoiesis of indeterminate potential were detected in 27% of the cohort, with TP53, KRAS, and KMT2C being the most frequently altered genes. There were no observed differences in the sensitivity of monitoring MRD using ddPCR or amplicon-based NGS (p = 1). Ultimately, 41% of the patients harbored potentially targetable alterations at diagnosis. CONCLUSION: The germline testing method not only enhanced sequencing results and raised the proportion of patients eligible for plasma monitoring, but also uncovered the existence of pathogenic germline variations, thereby aiding in the identification of patients at a higher risk of hereditary cancer syndromes.

Three-dimensional endoanal ultrasound to assess the validity of Goodsall's Rule and the Midline Rule in predicting the path of perianal fistula-in-ano and the location of the internal opening.

BACKGROUND: Correct identification of the internal opening is essential in the management of perianal fistulae. The aim of this study was to assess the validity of Goodsall's Law and the Midline Rule in predicting the path of perianal fistula-in-ano and the location of the internal opening using 3-dimensional endoanal ultrasound. METHODS: An observational study including patients diagnosed with fistula-in-ano, at our institution from January 2006 to December 2020 was performed. Location and distance from the anal verge of the external opening, internal opening, and the path of the fistulous tract were recorded during physical examination and endoanal ultrasound. Goodsall's and Midline rules were applied to all fistulae according to the location of the external opening. The location of the internal opening as predicted by either rule was then compared to the real location of the internal opening identified during endoanal ultrasound examination. RESULTS: Nine hundred and nine patients [657 (72.3%) males, mean age 50.78 (49.84-51.72) years] were included. 665 (73.2%) of fistulae were transsphinteric. Concordance between predicted internal opening site and the true internal opening location was 0.601 (good match) for Goodsall's rule, and 0.416 (moderate match) for the Midline rule. Goodsall's rule proved to be more predictive in the anterior plane (p < 0.001). Both rules were more likely to make a correct diagnosis in posterior fistulae located 4.5-7.5 mm from the anal verge. CONCLUSIONS: Both Midline and Goodsall's rules are highly predictive of the course of fistula tracts located in the posterior plane, and are lower for anterior located fistulae, female patients and when the external opening is located further from the anal verge.

Does delaying curative surgery for colorectal cancer influence long-term disease-free survival? A cohort study.

BACKGROUND: Surgical wait list time is a major problem in many health-care systems and its influence on survival is unclear. The aim of this study is to assess the impact of wait list time on long-term disease-free survival in patients scheduled for colorectal cancer resection. MATERIALS AND METHODS: A prospective study was carried out in patients with colorectal cancer scheduled for surgery at a tertiary care center. Wait list time was defined as the time from completion of diagnostic workup to definitive surgery and divided into 2-week intervals from 0 to 6 weeks. The outcome variables were 2-year and 5-year disease-free survival. RESULTS: A total of 602 patients, 364 (60.5%) male, median age 73 years (range = 71) were defined. The median wait list time was 28 days (range = 99). Two and 5-year disease-free survival rates were 521 (86.5%) and 500 (83.1%) respectively. There were no differences in 2-year or 5-year disease-free survival for the whole cohort or by tumor stage between wait list time intervals except for AJCC stage II tumors which showed a higher 5-year disease-free survival for the 2-4 and 4-6-week wait list time interval (p = 0.021). CONCLUSIONS: Time from diagnosis to definitive surgery up to 6 weeks is not associated with a decrease in 2-year or 5-year disease-free survival (DFS) in AJCC stage I through III colorectal cancer patients. These are important findings in the light of the COVID-19 pandemic and offer a window of opportunity for preoperative optimization and prehabilitation.

Impact of the novel powered circular stapler on risk of anastomotic leakage in colorectal anastomosis: a propensity score-matched study.

BACKGROUND: Several risk factors for anastomotic leakage (AL) following colorectal surgery have been described. Improvement in devices for performing anastomosis is a modifiable factor that could reduce AL rates. The aim of this study was to assess the impact of technical improvements in the Echelon Circular™ powered stapler (ECPS) on the left-sided colorectal AL rate compared to current manual circular staplers (MCS). METHODS: A cohort study was carried out on consecutive patients between January 2017 and February 2020 in whom left-sided stapled colorectal anastomosis above 5 cm from anal verge was performed. The primary end point was the risk of AL depending on the type of circular stapler used. The ECPS cases were matched to MCS cases by propensity score matching to obtain comparable groups of patients. RESULTS: Two hundred seventy-nine patients met the inclusion criteria. A MCS anastomosis was performed in 218 patients and ECPS anastomosis in 61 (21.9%). Overall, AL was observed in 25 (9%) cases. Factors significantly associated with AL were American Society of Anesthesiologists score (p = 0.025) and type of circular stapler used (p = 0.021). After adjusting the cases with propensity score matching (119 cases MCS versus 60 ECPS), AL was observed in 14 (11.8%) patients in MCS group and in 1 (1.7%) patient in the ECPS group (p = 0.022). AL in the MCS group required reoperation in seven cases (5.8%), the remaining seven patients were treated conservatively. The patient in the ECSP group required an urgent Hartmann's procedure CONCLUSIONS: The ECPS device could have a positive impact by reducing AL rates in left-sided colorectal anastomosis. Multicenter controlled trials are needed for stronger evidence to change practice.

Outcomes of Hartmann's procedure and subsequent intestinal restoration. Which patients are most likely to undergo reversal?

BACKGROUND: Aim of the study was to describe characteristics and outcomes of Hartmann's procedure (HP) and subsequent intestinal restoration. METHODS: Retrospective study including all patients who underwent HP over a period of 16 consecutive years. We propose a classification and regression tree for a more accurate view of the relationship between the variables related to intestinal restoration and their weighting in the decision to reverse HP. RESULTS: 533 patients were included. Overall morbidity rate of HP was 53.5% and mortality 21.0%. Overall morbidity of the intestinal continuity reconstruction was 47.3% and mortality 0.9%. Patients with a benign disease, aged under 69 years and with low comorbidity, had an 84.4% probability of undergoing intestinal reconstruction. CONCLUSIONS: HP is associated with high morbidity and mortality. Restoration of intestinal continuity involves minor, but frequent, morbidity and a low mortality rate. Age and comorbidities can decrease, and even override, the decision to reverse HP.

Propensity score analysis of postoperative and oncological outcomes after surgical treatment for splenic flexure colon cancer.

PURPOSE: The surgical treatment of splenic flexure colon cancer (SFCC) is somehow not yet well standardized. Postoperative and oncological results of the three surgical techniques most commonly used to treat SFCC: extended right colectomy (ERC), egmental left colectomy (SLC), and left colectomy (LC) were evaluated. METHODS: The study included all patients with stage I-III SFCC treated by ERC, SLC, or LC between 2005 and 2016. Postoperative and long-term outcomes after the different surgical techniques were analyzed: Propensity score matching (PSM) was performed to compare the outcomes between these surgical techniques and survival analyses were performed using the Kaplan-Meier method and log-rank tests. RESULTS: A total of 170 SFCC patients were operated; ERC was performed in 71 (41.76%), SLC in 36 (21.18%), and LC in 63 (37.06%). There were no significant differences in the short and long-term postoperative outcomes. Three comparison groups were developed so that PSM could be performed between the surgical technique cases: ERC (n = 59) vs. LC (n = 50); ERC (n = 50) vs. SLC (n = 33); and SLC (n = 32) vs. LC (n = 44). No differences in the short or long-term outcomes of these techniques were observed. CONCLUSION: The short and long-term outcomes between ERC, SLC, and LC are similar. SLC should be considered oncologically as appropiate as the other more extensive resections.

Reversal of Hartmann's procedure: a single-centre experience of 533 consecutive cases.

AIM: Hartmann's procedure (HP) is common. However, restoration of intestinal continuity is not so frequent. The aim of this study was to determine predictive factors which might influence outcomes following the reversal of HP. METHOD: All consecutive patients who underwent elective and emergency HP in a single institution between January 1999 and December 2014 were included. Data concerning patient, disease and treatment features were collected. Univariate and multivariate binary logistic regression models were used to determine prognostic factors. RESULTS: A total of 533 consecutive patients underwent HP over the 16-year period. Factors that were associated with a higher probability of reversal were age (< 69 years), American Society of Anesthesiologists (ASA) grade (I or II), indication for HP (likelihood of anastomotic leakage) and length of rectal stump reaching or exceeding the sacral promontory. A reduced probability of intestinal reconstruction was associated with anal incontinence, Stage IV cancer, postoperative transfusion or elective surgery. CONCLUSION: Age, ASA grade, the indication for HP, the length of rectal stump, anal incontinence, tumour stage, postoperative transfusion and elective surgery determine the probability of reversal.

Factors related to lymph node harvest: does a recovery of more than 12 improve the outcome of colorectal cancer?

AIM: The nodal harvest was studied to identify factors that affected the number of lymph nodes (LNs) retrieved in patients undergoing curative surgery for colorectal cancer. The influence of predictive factors on overall and disease-free 5-year survival was analysed. METHOD: All patients diagnosed with colorectal cancer who underwent oncological resection consecutively from January 1996 to December 2011 in a single institution have been studied. Factors influencing LN retrieval were analysed. A logistic regression analysis was performed to determine the factors that predicted a recovery of more than 12 LNs. A Cox regression analysis was made to identify the predictive factors of overall and disease-free 5-year survival. RESULTS: A total of 1166 patients were included in the study. The factors associated with the number of LNs harvested in surgical resections were age, colorectal surgeon, right colectomy, total colectomy, year of surgery, number of LN metastases and lymphocyte response. The factors that predicted a recovery of ≥ 12 LNs were age < 60 years, right colectomy, year of surgery and expert pathologist. A recovery of ≥ 12 LNs did not show significant differences in overall and disease-free 5-year survival, but the factor of colorectal surgeon did. CONCLUSION: Number of LN metastases, lymphocyte response, type of surgical resection, age of patient and colorectal surgeon can predict the LN harvest. Survival in colorectal cancer, however, is probably more influenced by the performance of the operation by an expert surgeon than by recovery of more than 12 LNs.

Long-term results of artificial bowel sphincter for the treatment of severe faecal incontinence. Are they what we hoped for?

OBJECTIVE: This study evaluates the long-term morbidity, functional results and quality of life (QOL) after treatment of severe faecal incontinence (FI) with the Acticon Neosphincter (American Medical Systems, Minneapolis, Minnesota, USA). METHOD: Between 1996 and 2002, 17 consecutive patients (14 female, 3 male; median age 46) underwent sphincter implantation. Clinical evaluation, incontinence severity and QOL were assessed. Anorectal manometry, endoanal ultrasound and pudendal nerve latency were performed preoperatively and at several stages of follow-up. The study was completed in December 2007. RESULTS: Mean follow-up was 68 months (range: 3-133). Morbidity occurred in 100% of patients from which 65% required at least one re-operation. After the first implant, 11 devices had to be removed (65%). Seven patients had a new implant. At the final stage, Acticon was activated in 9 cases (53%). Severity of FI improved from a median of 17.5 preoperatively to 9 (P = 0.005), 5.5 (P = 0.005) and 10 (P = 0.092) at 6, 12 months and at the end of follow-up, respectively. There was a significant improvement in QOL in all postoperative controls (P < 0.05). Severity of FI did not show a correlation with QOL in the preoperative period, but did at 6, 12 months and at the end of follow-up. Mean maximum resting pressure significantly increased with the full anal cuff. CONCLUSION: There is a high rate of morbidity, surgical re-interventions and explants after Acticon implant. Patients should be clearly informed about this before surgery. However, patients who have not had Acticon Neosphincter explanted, experience a significant improvement in anal continence and QOL.

The effect of surgery on quality of life in patients with faecal incontinence of obstetric origin.

OBJECTIVE: To evaluate the results of surgery in the treatment of faecal incontinence of obstetric origin and assess the effect of treatment on the quality of life of these patients. PATIENTS AND METHODS: A consecutive series of 43 patients, who had undergone surgery for severe faecal incontinence of obstetric aetiology between March 1990 and March 2004, was studied. The following studies were carried out: clinical evaluation, anorectal manometry, anal endosonography (from 1996 on) and measurement of the pudendal nerve terminal motor latency. The degree of incontinence, both preoperative and at the end of follow-up was evaluated using the Cleveland Clinic Score (CCS). Quality of life assessment was made using the Fecal Incontinence Quality of Life Scale (FIQL). RESULTS: The study was completed on 35 (87%) of the 43 patients. The mean age in the series was 53 years, (range 28-73). After an average follow-up of 50.4 months (range 4-132) the mean CCS had reduced significantly, passing from 16 (range 8-20) to 6 (range 0-18; P < 0.001). Pudendal neuropathy was found to be a factor of poor prognosis. The results of the quality of life questionnaire at the end of follow-up were: lifestyle 3.5 (SD 0.65), coping/behaviour 3.1 (SD 0.81), depression/self perception 3.7 (SD 0.75) and embarrassment 3.3 (SD 0.91). There is a statistically significant linear relationship between incontinence measured on the CCS and quality of life. For the 14 patients undergoing surgery since the publication of the FIQL questionnaire, it was possible to complete the questionnaire preoperatively, with significant improvement found on each of the four scales (lifestyle 1.7 vs 3.5; coping/behaviour 1.4 vs 3.2; depression 2.2 vs 3.8; embarrassment 1.8 vs 3.2; P < 0.001). CONCLUSION: Surgical treatment of faecal incontinence of obstetric origin achieves good results in a high percentage of patients and has a positive effect on their quality of life. The existence of prolonged preoperative pudendal nerve motor latency indicates a poor prognosis.

Experience and results on the surgical and medical treatment of ischaemic colitis.

OBJECTIVE: To analyse differences between patients with transient forms of ischemic colitis managed with medical treatment and those developing gangrenous forms subsidiaries of surgical treatment. MATERIAL AND METHODS: Retrospective study (1991-1998) of the ischemic colitis cases occurred in our center separating into two groups according to treatment received (A group: medical, 19 patients; B group: surgical, 10 patients). RESULTS: Hypertension mainly appear in B group being average age higher in this group than in A group (p < 0.05). Other risk factors analysed such as diabetes, cardiovascular disease, renal failure or consume of different drugs appear in similar way in both groups. In A group patients clinical presentation hematochezia is typical while B group use to start with acute abdomen associated to abdominal distension and hyperleukocytosis (p < 0.05). In group B average estance, morbidity and mortality have been higher than in A (17.4 vs 8.6 days 70 vs 5%, 40 vs 0%, respectively). CONCLUSION: Hypertension and advanced age are associated risk factors of gangrenous ischemic colitis. The classic clinical presentation of abdominal pain and hematochezia is typical in transient forms. Patients who need a surgical operation for ischemic colitis have a high morbimortality.

Experiencia y resultados en el tratamiento quirúrgico y conservador de la colitis isquémica / Experience and results on the surgical and medical treatment of ischaemic colitis

Objetivo: analizar las diferencias entre los pacientes con formas transitorias de colitis isquémicas (CI) resueltas con tratamiento médico y aquéllos que desarrollan formas gangrenosas subsidiarias de tratamiento quirúrgico. Material y métodos: se estudian retrospectivamente (19911998) los casos de CI en nuestro centro dividiéndolos en dos grupos según el tratamiento recibido (grupo A: conservador, 19 pacientes; grupo B: quirúrgico, 10 pacientes).Resultados: la hipertensión arterial aparece mayoritariamente en el grupo B siendo en éste la edad media superior respecto al grupo A (p<0,05). Otros factores de riesgo analizados como diabetes, patología cardiovascular, insuficiencia renal o consumo de diversos fármacos aparecen de forma similar en ambos grupos. En la presentación clínica de los pacientes del grupo A es típica la hematoquecia mientras que los del grupo B suelen debutar con abdomen agudo asociado a distensión abdominal y leucocitosis (p<0,05). En el grupo B han sido superiores la estancia media, la morbilidad y la mortalidad respecto al grupo A (17,4 vs 8,6 días, 70 vs 5 por ciento y 40 vs 0 por ciento, respectivamente). Conclusiones: la HTA y la edad avanzada son factores de riesgo asociados a CI gangrenosas. La presentación clínica clásica de dolor abdominal con hematoquecia es típica de las formas transitorias. Los pacientes que requieren intervención quirúrgica por CI tienen una elevada morbimortalidad (AU)